1. Field of the Invention
This invention relates to the use of cyclodextrins as carriers for active agents, for example drugs, labels, and the like. More specifically, it concerns the use of cyclodextrins as carriers for these active agents in combination with biospecific molecules such as proteins covalently bound to the cyclodextrins. The biospecific molecules facilitate delivery of the active agents to particular sites recognized by the biospecific molecules.
2. Background Information
The present invention employs cyclodextrins to carry active agents. Three monographs concerning cyclodextrins are Cyclodextrins and Their Inclusion Complexes, by J. Szejtli (Academiai Kiado, Budapest, 1962); Proceeding of the 1st International Symposium on Cyclodextrins, edited by J. Szejtli (D. Reidel Pub. Co., Dordrecht, Holland); and Cyclodextrin Chemistry, by M. L. Bender et al. (Springer-Verlag, Berlin, 1978). These three references provide a great deal of information on the preparation and properties of the cyclodextrin materials which are used as fundamental feedstocks in the present invention.
A number of systems have been proposed heretofore for delivering active agents to biologically recognizable sites. A "biologically recognizable site" is an organic group, usually a protein, or a molecule or larger organic structure which is capable of reacting with a second organic group, again usually a protein to form a unique complex. The wide range of events by which particular biologically recognizable sites uniquely complex with other molecules can include antibody-antigen interactions, hormone-receptor interactions, enzyme-substrate interactions and the like. The two groups which interact with one another can be termed a "biorecognition pair".
In these prior systems, the vector half of a biorecognition pair can carry an active agent such as a label, a drug, a toxin, or the like and through the biorecognition event specifically deliver this active agent to the other half of the pair which is present as part of an organism. In many cases heretofore, the active agent has been covalently bonded to the group which forms the vector half of the biorecognition pair. While this can work in some cases, in others, the cost and difficulties of making the covalent attachment are unacceptable, or the covalent attachment disturbs the properties of the active agent being delivered. In accord with the present invention, a universal carrier system is provided. This system has the advantage of not involving covalent bonding of the active agent to the biorecognition member.
Another advantage of this construction involves solubility issues. Many agents that are to be attached to biorecognition proteins are hydrophobic molecules. Their attachment decreases the solubility of the biorecognition molecule. Cyclodextrins confer increased solubility to the proteins and also help solubilize the complexed agent. Other hydroxyls on the cyclodextrins can be further derivatized to increase solubility if necessary.